Critical illness and sepsis are associated with significant morbidity and mortality, especially in conditions where existing therapeutic strategies remain suboptimal, such as in necrotizing fasciitis with shock. The pathophysiology of necrosis and organ dysfunction in necrotizing fasciitis is attributed to inflammation mediated by exotoxin-mediated cytokine cascade. Intravenous immunoglobulin neutralizes superantigen mediated exotoxin released by Group A Streptococcus and Staphylococcus aureus (principal causes of monomicrobial necrotizing fasciitis). In a large propensity-matched cohort of patients with necrotizing fasciitis and shock at 130 US hospitals, we found that IVIG use was sporadic (4%) and did not improve survival. These findings were subsequently coroborated by others in a randomized clinical trial (INSTINCT study Madsen et al, Intensive Care Med.2017 Apr 18). Antibiotic overuse remains a significant problem in the critically ill and is associated with toxicity and development of antimicrobial resistance. We found that a third of patients admitted with smoke-inhalation associated acute lung injury at 68 US hospitals are receiving antibiotics. Using modelling, we determined that such empiric therapy was not associated with improved outcomes, and as such, this practice should be discouraged. Among critically ill patients with suspected or confirmed sepsis in a larger cohort of US hospitals, we found that use of procalcitonin significantly reduced duration of antibiotic use without worsening outcomes. Most estimates of sepsis incidence and mortality in existing literature are estimated using claims data. Unfortunately claims based data are subject to a variety of biases. We estimate 10-year trends in the incidence and outcome of septic shock using clinical indicators in a cohort of academic medical centers in the United States and compared it to estimates obtained using claims based data. We found that the prevalence of septic shock was rising and mortality declining over time, albiet, both less vigorously than suggested by claims based methods.